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@ARTICLE{Tang:182766,
author = {W. C. Tang and S. W. Tsao and G. E. Jones and X. Liu and M.
H. Tsai and H.-J. Delecluse$^*$ and W. Dai and C. You and J.
Zhang and S. C. M. Huang and M. M. Leung and T. Liu and Y.
P. Ching and H. Chen and K. W. Lo and X. Li and C. M. Tsang},
title = {{L}atent {M}embrane {P}rotein 1 and macrophage-derived
{TNF}α synergistically activate and mobilize invadopodia to
drive invasion of nasopharyngeal carcinoma.},
journal = {The journal of pathology},
volume = {259},
number = {2},
issn = {0022-3417},
address = {Bognor Regis [u.a.]},
publisher = {Wiley},
reportid = {DKFZ-2022-02906},
pages = {163-179},
year = {2023},
note = {2023 Feb;259(2):163-179},
abstract = {Invadopodia are actin-rich membrane protrusions that digest
the matrix barrier during cancer metastasis. Since the
discovery of invadopodia, they were visualized as localized
and dot-like structures in different types of cancer cells
on top of a 2D matrix. In this investigation of Epstein-Barr
virus (EBV)-associated nasopharyngeal carcinoma (NPC), a
highly invasive cancer frequently accompanied by neck lymph
node and distal organ metastases, we revealed a new form of
invadopodium with mobilizing features. Integration of
live-cell imaging and molecular assays revealed the
interaction of macrophage-released TNFα and EBV-encoded
latent membrane protein 1 (LMP1) in co-activating the
EGFR/Src/ERK/cortactin and Cdc42/N-WASP signaling axes for
mobilizing the invadopodia with lateral movements. This
phenomenon endows the invadopodia with massive degradative
power, visualized as a shift of focal dot-like digestion
patterns on a 2D gelatin to a dendrite-like digestion
pattern. Notably, single stimulation of either LMP1 or TNFα
could only enhance the number of ordinary dot-like
invadopodia, suggesting that the EBV infection sensitizes
the NPC cells to form mobilizing invadopodia when
encountering a TNFα-rich tumor microenvironment. This study
unveils the interplay of EBV and stromal components in
driving the invasive potential of NPC via unleashing the
propulsion of invadopodia in overcoming matrix hurdles. This
article is protected by copyright. All rights reserved.},
keywords = {Epstein-Barr virus infection (Other) / invadopodia (Other)
/ invasion (Other) / latent membrane protein 1 (Other) /
live-cell imaging (Other) / nasopharyngeal carcinoma (Other)
/ tumor-associated macrophage (Other)},
cin = {F100},
ddc = {610},
cid = {I:(DE-He78)F100-20160331},
pnm = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
pid = {G:(DE-HGF)POF4-316},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36420735},
doi = {10.1002/path.6036},
url = {https://inrepo02.dkfz.de/record/182766},
}